Biomedical subjects
Publications and source records attributed to M Sone.
Five cases of cavernous hemangioma with fluid-fluid levels on magnetic resonance imaging and/or computed tomography are reported. The signal characteristics were those of blood and histological analysis of the fluid-fluid levels showed that they were blood-filled cavities in the tumor. Although this finding itself is not specific, it may help in confirming the diagnosis of cavernous hemangioma.
C-type natriuretic peptide (CNP) in human adrenal glands and adrenal tumors was measured with a specific radioimmunoassay for CNP. Tissue immunoreactive (IR-) CNP concentrations were 0.54 +/- 0.40 pmol/g wet tissue (gwt) (mean +/- SD) in 14 pheochromocytomas, 0.69 +/- 0.19 pmol/gwt in six adrenocortical tumors, and 0.49 +/- 0.22 pmol/gwt in seven normal adrenal glands (cortex and medulla mixed). These concentrations were comparable to those found in tissues from human brains. Sephadex G-50 superfine column chromatography and reverse-phase high performance liquid chromatography revealed that IR-CNP in normal adrenal glands and pheochromocytoma consisted of at least two components: a component in low molecular weight form chromatographically identical to CNP-22 and the other, a high molecular weight form very similar to human CNP-53. This study has shown that IR-CNP is present in human adrenal glands and adrenal tumors with similar molecular forms and comparable concentrations to those in the human brain.
1. C-type natriuretic peptide is a neuropeptide, which is also produced by the vascular endothelial cells. Plasma immunoreactive C-type natriuretic peptide concentrations in patients with various diseases have not yet been studied. 2. Plasma immunoreactive C-type natriuretic peptide concentrations were studied by radioimmunoassay in normal subjects, patients with congestive heart failure, non-dialysed patients with chronic renal failure and haemodialysis patients with chronic renal failure. The C-type natriuretic peptide levels were compared with the levels of atrial natriuretic peptide and brain natriuretic peptide. 3. Plasma immunoreactive C-type natriuretic peptide concentrations were greatly elevated in patients with chronic renal failure [non-dialysed, 13.0 +/- 4.2 pmol/l (mean +/- SEM), n = 9, P < 0.01 compared with normal subjects (4.4 +/- 0.4 pmol/l, n = 26); haemodialysis, 16.1 +/- 2.1 pmol/l, n = 13, P < 0.01], but not in patients with congestive heart failure (New York Heart Association Class II-IV, 3.0 +/- 0.7 pmol/l, n = 11, P > 0.05). Plasma immunoreactive atrial natriuretic peptide and brain natriuretic peptide concentrations were elevated both in patients with congestive heart failure and in haemodialysis patients with chronic renal failure. 4. Reverse-phase high performance liquid chromatography showed that immunoreactive C-type natriuretic peptide in plasma from normal subjects and haemodialysis patients was eluted in the positions of C-type natriuretic peptide-22 and -53. 5. These findings suggest that C-type natriuretic peptide is a non-cardiac circulating hormone and participates in the cardiovascular regulation in a different manner from atrial natriuretic peptide and brain natriuretic peptide.
We studied the presence of three natriuretic peptides--atrial natriuretic peptide (ANP), human brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP)--in the human kidney by radioimmunoassay and immunocytochemistry. Immunoreactive ANP, immunoreactive human BNP, and immunoreactive CNP concentrations in six kidneys were 0.12 +/- 0.07 (mean +/- SD), 0.23 +/- 0.08, and 0.37 +/- 0.07 pmol/g wet wt, respectively. Sephadex G-50 superfine column chromatography and reversed-phase high-performance liquid chromatography of kidney extracts revealed a broad peak of immunoreactive ANP comigrating with ANP-28 and urodilatin. Renal immunoreactive human BNP consisted of three components; the major component comigrated with human BNP-32. Renal immunoreactive CNP consisted of at least two components; the major component comigrated with CNP-22, and the minor component eluted in a position similar to that of authentic human CNP-53. Immunocytochemistry showed that immunoreactive human BNP was colocalized with immunoreactive ANP in the segments of distal tubules, whereas immunoreactive CNP was found predominantly in the proximal tubules. These findings indicate that these three natriuretic peptides are present in the human kidney and raise the possibility that they form a renal natriuretic peptide system that participates in the local regulation of sodium and water transport and renal circulation in the human kidney.
A subline of the NZB mouse, NZB/kl, was found to develop severe hearing disturbances at high frequency sound at the age of 4 to 6 months. Deposition of IgG was observed on the capillary wall of the stria vascularis of the mice, but the concentration of circulating immune complex did not seem to be correlated to the deposition. Electron microscopic examination revealed that the capillaries had a thick basement membrane, and in severe cases the membrane contained foamy structures of various size. In some cases the base membrane was so thick that the capillary lumen was narrowed, and the intermediate cells seemed to be damaged. No pathological findings were found in other inner ear tissues. These results suggest that the changes in the stria vascularis were possibly caused by an autoimmune mechanism which resulted in hearing disturbance.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a 38 amino acid peptide originally isolated from ovine hypothalamus. It has a potent stimulatory action on adenylate cyclase in the rat pituitary. The presence of PACAP was studied in the tumor tissues of ganglioneuroblastoma and neuroblastoma by radioimmunoassay and immunocytochemistry. Immunocytochemical studies showed positive immunostaining in 4 out of 7 ganglioneuroblastomas and 4 out of 6 neuroblastomas. Immunoreactive PACAP concentrations in tissues of 3 ganglioneuroblastomas ranged from 14.5 to 27.8 pmol/g wet weight (20.0 +/- 5.7 pmol/g wet weight, mean +/- S.D.) and the concentration in one neuroblastoma tissue was 111.0 pmol/g wet weight. Reverse phase high performance liquid chromatography of the tumor tissue extract of ganglioneuroblastoma showed a peak eluting in the position of PACAP1-38 and smaller broad peaks eluting later. These results indicated that high concentrations of immunoreactive PACAP were present in the tumor tissues of ganglioneuroblastoma and neuroblastoma, and suggest the possibility that this peptide plays a pathophysiological role in some ganglioneuroblastomas and neuroblastomas.
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Initial experimental and clinical studies have indicated that 5-fluorouracil (5-FU) toxicity can be reduced by delivering 5-FU at around 4 a.m. More recent data have suggested that the toxicity might be reduced even more with delivery at around 9-10 p.m. The current study determined the maximum tolerated dose (MTD) for 5-FU and leucovorin (LV) delivered as a continuous circadian infusion over 14 days every 28 days, with the peak of the infusion occurring at around 3-4 a.m. The peak drug delivery was shifted to 9-10 p.m. in all patients developing toxicity of > or = grade II (Eastern Cooperative Oncology Group) to determine if this timing further reduced toxicity and enabled increased dose intensity. A total of 14 patients with metastatic adenocarcinoma received an admixture of 5-FU and LV via a programmable portable infusion pump, with 62.5% of the 24-h dose being given over 7 h around the infusion peak. The starting dose level of 5-FU (200 mg/m2 daily) and LV (5 mg/m2 daily) was that established as the highest tolerable dose rate in a previously reported phase I study using a 14-day flat infusion of 5-FU and LV. The LV dose was first escalated to 20 mg/m2 daily, followed by escalations of the 5-FU dose. A total of 51 courses were evaluable for toxicity. The dose-limiting toxicity was oral mucositis and hand-foot syndrome. More dose intensity could be delivered using a circadian infusion peaking at around 3-4 a.m. than was possible with a flat infusion of these drugs. Toxicity was reduced even further with peak drug delivery at around 9-10 p.m. The recommended dose for phase II studies using this schedule is 250 mg/m2 5-FU daily and 20 mg/m2 LV daily with the peak of the infusion occurring at 9-10 p.m. This is a 300% and 25% higher dose for LV and 5-FU, respectively, than was found to be safe for a flat infusion.
The Bar locus of Drosophila is known to be a small complex consisting of two similar homeobox genes, BarH1 and BarH2. Using egr as an ommatidium marker, possible mechanisms of formation of malformed eyes were examined. As in the case of BarH1, overexpression of BarH2 was found to be capable of inducing Bar-like eye malformation. It was suggested that suppression of the anterior progression of the morphogenetic furrow and inhibition of reinitiation of normal ommatidial differentiation were mandatory to formation of the reduced eye morphology in Bar mutants.
1. Elevation of blood pressure is one of the major side effects of recombinant human erythropoietin therapy in haemodialysis patients. 2. We investigated the possible involvement of endothelin in the pathogenesis of this recombinant human erythropoietin-induced blood pressure elevation in 51 patients undergoing maintenance haemodialysis. 3. Blood haemoglobin level increased from 7.1 +/- 0.1 to 8.8 +/- 0.1 g/dl (means +/- SEM) after 8 weeks of treatment with recombinant human erythropoietin (3000-4500 units/week). An increase in mean blood pressure was found in 19 patients (37%) (n = 9, by 0-10 mmHg; n = 10, by > 10 mmHg). 4. Plasma immunoreactive-endothelin concentration significantly increased from 2.26 +/- 0.18 to 3.14 +/- 0.31 pmol/l in the 10 patients whose mean blood pressure increased by more than 10 mmHg (P < 0.05), but not in the other patients. Moreover, the increase in plasma immunoreactive-endothelin concentration showed a significant positive correlation with the change in mean blood pressure in 19 patients with elevated mean blood pressure (r = 0.47, P < 0.05). 5. There was no significant correlation between the change in plasma immunoreactive-endothelin concentration and the change in blood haemoglobin level or the change in body weight. 6. These results suggest the possibility that endothelin may contribute to the recombinant human erythropoietin-related rise in blood pressure in some haemodialysis patients.
The presence of immunoreactive endothelin (ir-ET) in the tumor tissues of two cases of ectopic ACTH-secreting bronchial carcinoid tumors was studied by radioimmunoassay. The cross-reaction with big ET-1, ET-2, and ET-3 was 5%, 6%, and 6%, respectively. Tumor tissue ir-ET concentrations in two ectopic ACTH-secreting bronchial carcinoid tumors were 920 and 3,370 fmol/g wet weight, which were much higher than those in pheochromocytomas (146 +/- 70 fmol/g wet weight; n = 12, mean +/- SD), adrenocortical tumors (115 +/- 105 fmol/g wet weight, n = 14), and normal parts of adrenal glands (82 +/- 31 fmol/g wet weight, n = 12). High-performance liquid chromatography of the tumor tissue extract showed that the ir-ET was mainly eluted in the position of ET-1. Plasma levels of ir-ET in these two cases were not elevated (1.2 and 1.7 pmol/L). The findings of the present study suggest that ET-1 has local pathophysiologic roles in the tumor tissues of ectopic ACTH-secreting bronchial carcinoid tumors.
A small area of changed signal intensity in the hippocampus is often seen on magnetic resonance (MR) images of the brain in patients without specific clinical signs or symptoms. To ascertain its cause by means of histologic examination, this finding was evaluated retrospectively in 109 patients and correlated with findings in two human brain specimens. This area of change was typically round or curvilinear and 1-2 mm in diameter. Its location was between the hippocampus and dentate gyrus. The signal intensity was the same as that of cerebrospinal fluid (CSF) with all MR sequences used. The incidence of change in signal intensity was greater in elderly patients. Correlation with histologic findings showed that this area of change, a dilated perivascular space, was the residual cavity of the hippocampal sulcus. Whenever an area of CSF-like signal intensity has this shape and topographic features, the possibility of anatomic variation should be considered before the change in signal intensity is diagnosed as brain injury.
The cells of the renal medulla adapt osmotically to high extracellular tonicities by high concentrations of organic osmolytes. Intracellular accumulation of these substances is, however, relatively slow. The aim of the present study was to assess the effect of an abrupt rise in extracellular tonicity on intracellular osmotically active substances after prior reduction of medullary contents of organic osmolytes by chronic diuresis. Intra- and extracellular electrolyte concentrations at the papillary tip and the tissue contents of methylamines (glycerophosphorylcholine, betaine), polyols (myo-inositol, sorbitol), and several amino acids were determined in the different kidney zones by electron microprobe analysis and high-performance liquid chromatography in control animals, in rats infused for 6 days with furosemide via osmotic minipumps, and in rats given the vasopressin analogue [deamino-Cys1,D-Arg8]vasopressin (DDAVP) after the chronic furosemide treatment. Chronic diuresis greatly reduced interstitial tonicity and inner medullary contents of methylamines and polyols and moderately reduced inner medullary amino acid contents but did not significantly affect intracellular electrolyte concentrations. When the diuretic rats were infused with DDAVP for 2 h, interstitial tonicity more than doubled and intracellular K and Cl concentrations rose by approximately 60 and 160%, while inner medullary contents of methylamines, polyols, and amino acids were not changed significantly. These data demonstrate that after effective depletion of medullary organic osmolytes by long-term diuresis, the cells of the renal papilla adapt osmotically to an abrupt increase in extracellular tonicities by elevated cell electrolyte concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
The presence of three regulatory peptides, corticotropin-releasing hormone, neuropeptide Y and endothelin-1, was studied by radioimmunoassay in the tumor tissue of an ACTH-secreting bronchial carcinoid. A 36-year-old female was admitted to hospital because of moon face, central obesity and hypertension. High levels of plasma ACTH and cortisol and urinary 17-OHCS and 17-KS were found. One mg dexamethasone did not suppress plasma ACTH and cortisol levels, but 8 mg did so slightly. Corticotropin-releasing hormone (100 micrograms, iv) stimulated plasma ACTH levels (0 min; 34.8 pmol/l; 30 min; 41.1 pmol/l). The computerized tomography showed the presence of a tumor in the right lung. This lung tumor was removed surgically and has been shown by microscopical examination to be a bronchial carcinoid with ACTH-positive cells. The tumor tissue concentrations of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 were 3.34 pmol/g wet weight, 8.07 pmol/g wet weight and 0.92 pmol/g wet weight, respectively, although plasma concentrations of these three peptides were not elevated. Reverse phase high performance liquid chromatography showed that immunoreactive peptides in the tumor tissue were mainly eluted in the position of the standard peptides. These findings indicate that this case of ACTH-secreting bronchial carcinoid had high levels of corticotropin-releasing hormone, neuropeptide Y and endothelin-1 in its tumor tissue and suggested that these peptides may act locally, in a paracrine or autocrine manner, in the tumor.
Fluid-fluid levels in bone tumors have been described in aneurysmal bone cysts and other cystic tumors of bones and soft tissue tumors. We experienced three bone tumors (simple bone cyst, bone metastasis, and osteosarcoma) and three soft tissue tumors (fibrosarcoma, two cases of cavernous hemangioma) that showed fluid-fluid levels on MR, and investigated their cause. Causes included blood in the cystic spaces, hemorrhage in the tumor, the telangiectatic component of the osteosarcoma, and the cavernous component of the hemangioma. No specific diagnosis could be made based on the finding of fluid-fluid levels. We conclude that fluid-fluid levels on MR are rather nonspecific findings in bone and soft tissue tumors and that the diagnosis should be made on the basis of other radiological and clinical findings.
Sodium absorption in distal tubule segments was stimulated by increasing the distal delivery via infusion of hypertonic saline. In these animals, and in control rats, electrolyte concentrations in thick ascending limb cells, light and dark cells of the collecting duct in the outer and inner stripe of the outer medulla and in cells of the proximal straight tubule (outer stripe only) were studied. The measurements were performed by electron microprobe analysis of freeze-dried cryosections of the outer medulla. In addition, organic osmolytes (glycerophosphorylcholine, betaine and myo-inositol) were measured by high performance liquid chromatography in cortex and outer medulla. Augmented delivery of sodium chloride to the distal tubule was associated with increased sodium concentrations of thick ascending limb cells both in the outer and inner stripe and of medullary collecting duct light and dark cells in the outer stripe. While the sum of organic osmolyte concentrations was 28% higher in the outer medulla of the salt-loaded animals compared with controls, this value was unchanged in the renal cortex. These findings indicate that the primary event underlying stimulation of sodium absorption along the thick ascending limb during increased distal sodium delivery is enhanced entry of sodium across the apical cell membrane. This would be expected to lead to higher cell sodium concentrations and stimulation of basolateral active Na-K-exchange. The enhanced transport activity of outer medullary tubules may be associated with increased interstitial tonicities and intracellular retention of organic osmolytes.
The production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells.
Electron microprobe analysis on freeze-dried cryosections was used to determine the effect of the loop diuretics torasemide and furosemide on intracellular electrolyte concentrations in individual cells of the outer and inner stripe of the outer medulla and on cell rubidium uptake, the latter a measure of basolateral Na-K-ATPase activity. In addition, the organic osmolytes glycerophosphorylcholine (GPC), betaine, inositol and sorbitol in cortex, outer medulla and inner medulla were measured using HPLC. Both loop diuretics significantly reduced sodium and chloride concentrations and rubidium uptake in thick ascending limb cells, but did not affect sodium concentration or rubidium uptake in the proximal straight tubule (PST) cells or in the light or dark cells of the outer medullary collecting duct (OMCD). Chloride concentrations in these cells (that is, PST cells, OMCD light and dark cells) were lowered by loop diuretics, albeit less than in thick ascending limb cells. Administration of both loop diuretics for only 20 minutes was sufficient to significantly depress tissue concentrations of GPC, betaine, and myo-inositol in the outer medulla and of GPC, betaine and sorbitol at the papillary tip. These results indicate that loop diuretics, presumably by blocking apical sodium entry, decrease thick ascending limb cellular sodium concentration and, as a consequence, reduce Na-K-ATPase activity as assessed by cell rubidium uptake. Although this has been shown previously in in vitro preparations, the present study confirms this for the first time in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)